Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
Jiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji Universi...
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Dove Medical Press
2023-09-01
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author | Lu J Yu N Liu Q Xie Y Zhen L |
author_facet | Lu J Yu N Liu Q Xie Y Zhen L |
author_sort | Lu J |
collection | DOAJ |
description | Jiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhen, Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86 1 582 108 9038, Email zhenleilei123@126.comIntroduction: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.Keywords: diabetes, periodontitis, macrophage, osteoclast differentiation |
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language | English |
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spelling | doaj.art-a739e6f4ab814fcd80ca384735e013e72023-09-21T19:08:58ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-09-01Volume 185327534286743Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice ModelLu JYu NLiu QXie YZhen LJiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhen, Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86 1 582 108 9038, Email zhenleilei123@126.comIntroduction: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.Keywords: diabetes, periodontitis, macrophage, osteoclast differentiationhttps://www.dovepress.com/periodontal-ligament-stem-cell-exosomes-key-to-regulate-periodontal-re-peer-reviewed-fulltext-article-IJNdiabetesperiodontitismacrophageosteoclast differentiation |
spellingShingle | Lu J Yu N Liu Q Xie Y Zhen L Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model International Journal of Nanomedicine diabetes periodontitis macrophage osteoclast differentiation |
title | Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model |
title_full | Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model |
title_fullStr | Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model |
title_full_unstemmed | Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model |
title_short | Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model |
title_sort | periodontal ligament stem cell exosomes key to regulate periodontal regeneration by mir 31 5p in mice model |
topic | diabetes periodontitis macrophage osteoclast differentiation |
url | https://www.dovepress.com/periodontal-ligament-stem-cell-exosomes-key-to-regulate-periodontal-re-peer-reviewed-fulltext-article-IJN |
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